Myeloablative I-131-tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age ≥ 60 years with B cell lymphoma

Abstract

Myeloablative therapy and autologous stem cell transplantation (ASCT) are underutilized in older patients with B cell non-Hodgkin (B-NHL) lymphoma. We hypothesized that myeloablative doses of (131)I-tositumomab could be augmented by concurrent fludarabine, based on preclinical data indicating synergy. Patients were ≥ 60 years of age and had high-risk, relapsed, or refractory B-NHL. Therapeutic infusions of (131)I-tositumomab were derived from individualized organ-specific absorbed dose estimates delivering ≤ 27 Gy to critical organs. Fludarabine was initiated 72 hours later followed by ASCT to define the maximally tolerated dose. Thirty-six patients with a median age of 65 years (range, 60 to 76), 2 (range, 1 to 9) prior regimens, and 33% with chemoresistant disease were treated on this trial. Dose-limiting organs included lung (30), kidney (4), and liver (2) with a median administered (131)I activity of 471 mCi (range, 260 to 1620). Fludarabine was safely escalated to 30 mg/m(2) × 7 days. Engraftment was prompt, there were no early treatment-related deaths, and 2 patients had ≥ grade 4 nonhematologic toxicities. The estimated 3-year overall survival, progression-free survival, and nonrelapse mortality were 54%, 53%, and 7%, respectively (median follow up of 3.9 years). Fludarabine up to 210 mg/m(2) can be safely delivered with myeloablative (131)I-tositumomab and ASCT in older adults with B-NHL.

Trial registration: ClinicalTrials.gov NCT00110071.

Keywords: Autologous; B cell lymphoma; Elderly; Radioimmunotherapy.

Conflict of interest statement

Conflict of interest:

Glaxo-Smith Kline provided study drug for this trial. DGM receives research funding from Glaxo-Smith Kline for a separate study. No other potential conflicts were identified.

Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Treatment schema. Note 3 patients were received 1.7mg/kg 131I-tositumomab.

Figure 2

A) Overall and progression free survival at median follow up of 3.9 years. B) Cumulative incidence of relapse and non-relapse mortality. C) Survival outcomes by B-cell lymphoma histology

Figure 2

A) Overall and progression free survival at median follow up of 3.9 years. B) Cumulative incidence of relapse and non-relapse mortality. C) Survival outcomes by B-cell lymphoma histology